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- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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- Abbafati, Cristiana, et al.
(författare)
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- 2020
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Tidskriftsartikel (refereegranskat)
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- Sabatini, S, et al.
(författare)
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International relevance of two measures of awareness of age-related change (AARC)
- 2020
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Ingår i: BMC geriatrics. - : Springer Science and Business Media LLC. - 1471-2318. ; 20:1, s. 359-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundA questionnaire assessing awareness of positive and negative age-related changes (AARC gains and losses) was developed in the US and Germany. We validated the short form of the measure (AARC-10 SF) and the cognitive functioning subscale from the 50-item version of the AARC (AARC-50) questionnaire in the UK population aged 50 and over.MethodsData from 9410 participants (Mean (SD) age = 65.9 (7.1)) in the PROTECT cohort were used to explore and confirm the psychometric properties of the AARC measures including: validity of the factor structure; reliability; measurement invariance across men and women, individuals with and without a university degree, and in middle age, early old age, and advanced old age; and convergent validity with measures of self-perception of aging and mental, physical, and cognitive health. We explored the relationship between demographic variables (age, sex, marital status, employment, and university education) and AARC.ResultsWe confirmed the two-factor structure (gains and losses) of the AARC-10 SF and the AARC-50 cognitive functioning subscale. Both scales showed good reliability and good convergent validity for AARC losses, but weak convergent validity for AARC gains. For both scales metric invariance was held for the two subgroups defined by education level and age. For the AARC-50 subscale, but not for the AARC-10 SF, strong invariance was also held for the two subgroups defined by sex. Age, sex, marital status, employment, and university education predicted AARC gains and losses.ConclusionsThe AARC-10 SF and AARC-50 cognitive functioning subscale identify UK individuals who perceive age-related changes in their mental, physical, and cognitive health.
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